Purpose<1>

In the daily medical practice and hospital/insurance
pharmacy activities it is not rare to encounter scenes inwhich patients complain of early symptoms of adverse
drug reactions.
In such a circumstance, each medical institution isworried about prompt and efficient responses within the
short examination/dosing time, but more importantly thiswould be considered the core of risk management ofpatients.
In this situation we have built a database that links
adverse reaction terms in the package inserts to drugs
with expressions of early symptoms of adverse reactions
patients complain of for efficiency of identifying the causaldrugs.
Copyright＠2003.ｄata Index Co.

Flow to Discoveries of Adverse DrugReactions
Rx.
1) Drug A 3 tablets a day after
each meal for 7 days2) Drug B 1 tablet a day after
breakfast for 30 days

I have developed<2>

Drug A isthe cause?!

It takes too much timeto investigate each package insert
to each drug prescribedrashes since I started
taking a drug….
<Package insert to Drug B>

Investigate package
inserts to respective
drugs prescribed<Package insert to Drug A>
Serious adverse drug reaction:
Stevens-Johnson syndrome

Copyright＠2003.ｄata Index Co.

Comparison with Conventional Approach < 3 >◆ Conventional◆◆Developed a database of adverse drug
reaction early symptoms◆

Complaint of early symptom of an adverse drug
reaction from patient/family/helper
Check details ofprescription

1) Enter terms based on the complaint
2) Output early symptoms of serious adverse
reactions of the prescribed drugs

Investigate the adverse drug
reaction in the package inserts
to respective drugs prescribed

Identify the causal drugIdentify the causal drug

Protect patients from serious risks
by providing convenient and swift
response, and appropriate drugtaking guidance！
Copyright＠2003.ｄata Index Co.

Features of Developed Database < 4 >Uniquely marked-up processing enables you to extract all adverse
drug reaction information described in the package inserts toprescription drugs as terms.
Extracted adverse drug reaction terms can be classified into “serious
adverse drug reactions” and “other adverse drug reactions”.
Early symptoms of an adverse drug reaction can be printed out andutilized as information for drug-taking guidance.
Easily identify the causal drug from the complaint of early symptomsof an adverse drug reaction from patient/family/helper and takeprompt responses.
The database is structured to allow convenient and regular
maintenance
Highly convenient
Copyright＠2003.ｄata Index Co.

System Flow
Put individual package
inserts to prescription
drugs into a database<5>

Master file of
医療用医薬品18,000 prescription
18,000品目のマスター
drugs

Process marking-up to
the adverse drug
reaction terms

List upadverse drug
reaction terms

Code adverse
drug reactiontermsPrepare early
symptoms

Classify andcode early
symptoms

List up serious
adverse drug
reactionsClassify andscrutinize serious
adverse drug
reaction terms

Processsynonymouswords

Copyright＠2003.ｄata Index Co.

Process Steps for Database Structure (1) < 6 >◆Mark-up processing of adverse drug reaction terms
in package inserts put in a database◆
Package insert

After mark-up
processing(1) Serious adverse drug reactions
1) Oculomucocutaneous syndrome (Stevens-Johnsonsyndrome), toxic epidermal necrolysis (Lyell syndrome)
Adequate observations should be provided, asoculomucocutaneous syndrome or toxic epidermal
necrolysis may occur. If such a syndrome occurs, stop
dosing and provide appropriate treatment.

1. Serious adverse reactions1). ¥¥61 Oculomucocutaneous syndrome ( 61 StevensJohnson syndrome) , 61toxic epidermal necrolysis (61Lyellsyndrome): Adequate observations should be provided, as
oculomucocutaneous syndrome or toxic epidermal necrolysis mayoccur. If such a syndrome occurs, 92 stop dosing == and provide
appropriate treatment.
Copyright＠2003.ｄata Index Co.

Process Steps for Database Structure (2) < 7 >◆Coding the terms tagged and carved out using Access◆Marked-up processed data

Assign a unique code to each termCoding

1. Serious adverse reactions1). ¥¥61 Oculomucocutaneous
syndrome (61 Stevens-Johnson
syndrome), 61toxic epidermal
necrolysis (61Lyell syndrome):
Adequate observations should beprovided, as oculomucocutaneous
syndrome or toxic epidermal necrolysis
may occur. If such a syndrome occurs,
92 stop dosing == and provide
appropriate treatment.

Early symptoms of adverse drug reactions K2: TablesStevens-Johnsonsyndrome
Stevens-Johnsonsyndrome
Oculomucocutaneoussyndrome

Copyright＠2003.ｄata Index Co.

Process Steps for Database Structure (3) < 8 >◆Linking synonymous words processing(hypernym/hyponym) with early symptoms of adverse drugreactions◆Enter early symptoms of adverse

Hypernym code
(Processing ofsynonymous words)

Unique code

Adverse drug reaction terms
marked up and extracted

drug reactions anticipated fromadverse drug reaction terms

Early symptoms of adverse drug reactions K2: Tables

Stevens-Johnson syndrome

Develop a fever, feel dull, articular pain, headache,have no appetite, entire skin inflames anddevelops a rash, have a blister, mucous
membrane such as in the mouth, in the nose or
conjunctiva festers, have a red eye

Stevens-Johnson syndrome

Oculomucocutaneous syndrome◎

Register early symptoms of adverse drug reactions, which are anticipated tobe major and occur at a high frequency, in plain words◎

Individual expressions are made to carve out by compartmentalizing “,(comma)”
Copyright＠2003.ｄata Index Co.

Classifying and Scrutinizing Adverse Drug
Reaction Terms<9>
All adverse drug reaction terms were shortlisted into terms
described in the ‘serious adverse drug reactions’ column:
2,083 words (as of August 2003)
Serious adverse drug reactions were classified andscrutinized
Serious adverse drug reaction terms: 1,010 words
Symptom terms: 711 words
Test terms: 265 words
Expressions of early symptoms were standardized andscrutinized
Regional classification of early symptoms is now being
developed in the light of convenience of use of information
printed out from a system in clinical field
Copyright＠2003.ｄata Index Co.

Database Structure (1)< 10 >

Microsoft Access - [Early symptoms of adverse drug reactions K2: Tables]
File (F) Edit (E) Visual (V) Insert (I) Format (O) Record (R) Tool (T) Window (W) Help (H)MS P Gothic

Stevens-Johnson Develop a fever, feel dull, articular
pain, headache, have no appetite,
syndrome
entire skin inflames and develops
a rash, have a blister, mucous
membrane such as in the mouth,in the nose or conjunctiva festers,
redness in the eye

Subjective

Subjective/objective

Feel dull, articular pain,
headache, have noappetite

Develop a fever, entire
skin inflames anddevelops a rash, have ablister, mucous membranesuch as in the mouth, inthe nose or conjunctiva
festers, redness in the eye

OthersTest data

Stevens-Johnson
syndrome* Excerpt from package insert to “Diclofenac
Sodium Tablet”
Oculomucocutaneous syndrome

record(filter)(1) Serious adverse drug reactions (frequencies unknown)
The following adverse reactions may occur.
In this case, stop dosing and provide appropriate treatment.
1) Shock (chest distress, cold sweat, dyspnoea, coldness of limbs, hypotension,
disturbance of consciousness, etc.), anaphylactoid symptoms (urticria,angioedema, dyapnoea, etc.)
2) Hemorrhagic shock or gastrointestinal ulcer associated with puncture3) Aplastic anemia, hemolytic anemia, agranulocytosis, thrombocytopenia4) Oculomucocutaneous syndrome (Stevens-Johnson syndrome), toxic
epidermal necrolysis (Lyell syndrome), erythroderma (exfoliative dermatitis)
5) Acute renal failure (nephritis interstitial, renal papillary necrosis, etc.)(Symptoms/test findings: oliguria, haematuria, proteinuria, BUN, increased
creatinine in blood, hyperkalemia, hypoalubuminemia, etc.), nephrotic
syndrome

Datasheetview

Copyright＠2003.ｄata Index Co.

Database Structure (2)< 11 >

Early symptoms of adverse drug reactions K2: Tables
Subjective
Hypercalcemia

Feel dull, have no appetite,
confused, have concentration
problems, feel sick, feel numb,jumped pulse, have high bloodpressure, feel thirsty

Feel dull, have noappetite, feel sick,feel thirsty

Subjective/objective
Have concentration
problems, jumpedpulse, feel numb

OthersConfused

Test data
Have high bloodpressure* Excerpt from package insert to “CalcitriolInjection”(1)

Seriousadversedrug
reactionsHypercalcemia (28.1%): Measure serum calcium values regularly(at least once two weeks), as this product increases serum calcium.
If the serum calcium value exceeds the upper limit of normal valuesof serum calcium set by the medical institution by 1 mg/dL,
immediately suspend dosing. Be careful about appearance ofsymptoms (itching paraesthesia, the back teeth, etc.) considered
due to hypercalcemia. Restart dosing only after the serum calcium
values are confirmed to be lowered to the normal values of serum
calcium set by the medical institution by suspension of dosing, andconsider lowering the dose with reference to the dose level before
suspension (Refer to the section of <precautions for use related todosageandadministration>).
Note 2) If the compensated calcium value exceeds 11.5 mg/dL

Copyright＠2003.ｄata Index Co.

Classification Criteria for Expressions of
Early Symptoms< 12 >
Item
Subjective
symptoms[457 expressions]

Subjective/objective
symptoms[654 expressions]Classification criteria

Early symptoms known only to patient
5 senses (sensuous expressions; pain, itching, others)
Desires (3 desires), etc.

Early symptoms known to patient andfamily/helper
Including change in excretion such as urine and stool,temporal course of events such as “I became unconscious”,
and symptoms cognizable as pointed out by others

Objective symptoms[75 expressions]

Early symptoms not recognizable bypatient but known only to family/helper

Test symptoms[81 expressions]

Symptoms to be tested as laboratory
values can only tell
* Number in [ ] as of March 2003

Copyright＠2003.ｄata Index Co.

Review< 13 >Quality medical service is in need although effectiveness ofmedical care is progressed, and recently ‘Secure rights andsafety of patients’ has been established as an independent item
for hospital function assessments. Specifically, in order toensure that information on adverse drug reactions that serves
as the central role of patient safety management is provided andthat safety measures are promptly and certainly provided
irrespective of experience of medical professionals, it isessential to utilize information technology. In this respect, thisdatabase is very helpful.
By loading this database to an application system easily usable
by medical professionals and presentable to patients in anunderstandable way, verification will be performed in various
medical fields to further improve the database on early
symptoms of adverse drug reactions.
Copyright＠2003.ｄata Index Co.